Preexposure prophylaxis for HIV infection among African women.
Preexposure prophylaxis for HIV infection among African women.
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DOI：
10.1056/nejmoa1202614
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发表时间：
2012-08-02
期刊：
影响因子：
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通讯作者：
FEM-PrEP Study Group
中科院分区：
文献类型：
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作者：
Van Damme L;Corneli A;Ahmed K;Agot K;Lombaard J;Kapiga S;Malahleha M;Owino F;Manongi R;Onyango J;Temu L;Monedi MC;Mak'Oketch P;Makanda M;Reblin I;Makatu SE;Saylor L;Kiernan H;Kirkendale S;Wong C;Grant R;Kashuba A;Nanda K;Mandala J;Fransen K;Deese J;Crucitti T;Mastro TD;Taylor D;FEM-PrEP Study Group
在一些试验中，抗逆转录病毒药物暴露前预防在预防人类免疫缺陷病毒（HIV）感染方面有效，但在其他试验中无效。在这项随机、双盲、安慰剂对照试验中，我们将肯尼亚、南非和坦桑尼亚的2120名HIV阴性女性分配为接受富马酸替诺福韦酯和恩曲他滨（TDF-FTC）或安慰剂联合治疗，每日一次。主要目的是评估TDF-FTC预防HIV感染的有效性和安全性。TDF-FTC组中有33名女性发生HIV感染（发病率为4.7/100人-年），安慰剂组中有35名女性发生HIV感染（发病率为5.0/100人-年），TDF-FTC组的估计风险比为0.94（95%置信区间为0.59至1.52; P = 0.81）。TDF-FTC组中恶心、呕吐或丙氨酸氨基转移酶水平升高的女性比例显著较高（分别为P = 0.04、P<0.001和P = 0.03）。TDF-FTC组因肝或肾异常而停药的发生率（4.7%）高于安慰剂组（3.0%，P = 0.051）。在TDF-FTC组中，不到40%的未感染艾滋病毒的妇女在与血清转换妇女的艾滋病毒感染窗口相匹配的访视中有最近使用避孕药的证据。由于缺乏疗效，该研究于2011年4月18日提前停止。与安慰剂相比，TDF-FTC预防治疗并没有显著降低HIV感染率，但副作用发生率增加。尽管有大量的咨询工作，药物依从性似乎很低。（由美国国际开发署和其他机构支持; FEM-PrEP ClinicalTrials.gov编号，NCT 00625404。
Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF–FTC in preventing HIV acquisition and to evaluate safety. HIV infections occurred in 33 women in the TDF–FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P = 0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF–FTC group (P = 0.04, P<0.001, and P = 0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF–FTC group (4.7%) than in the placebo group (3.0%, P = 0.051). Less than 40% of the HIV-uninfected women in the TDF–FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. Prophylaxis with TDF–FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.)